This application proposes to test genetic and nongenetic models for the inheritance of epilepsy. In this analysis, special emphasis will be placed on models that can account for the consistent finding in the literature that offspring of women with epilepsy are more likely to have epilepsy than are offspring of men with epilepsy. The target population will consist of clients from voluntary organizations for epilepsy. Data on seizure occurrence in the clients with epilepsy (probands) and in their first-degree relatives will be collected in a stuctured telephone interview, to be administered by members of the staffs of the organizations. Epilepsy diagnoses of the probands and their affected relatives will be confirmed by medical record reviews and by telephone interviews with the relatives themselves, when permission is obtained from the probands to contact their relatives. Heterogeneity in the familial distribution of epilepsy will be examinend by stratifying the probands by seizure type, etiology, and age at onset, and comparing risks of specific types of epilepsy in siblings and offspring of probands with different diagnoses. Risks of febrile convulsions and all seizure types combined will be compared only for offspring of probands with different diagnoses. Epidemiologic risk analysis will be used to distinguish between conventional genetic models and maternal transmission, while controlling for biases that could have created a spurious maternal excess in previous work. These biases include age differences between relatives in different comparison groups, reporting bias, fertility differences between male and female probands, and selective fertility of men with epilepsy. Segregation analysis, using both the transmission probability and mixed models, will be used to formally test goodness-of-fit of the data to various genetic models. Investigation of the mode of inheritance of familial epilepsy is important for understanding the factors that can increase seizure susceptibility. An understanding of the genetic or environmental mechanisms of transmissin of susceptibility to epilepsy could lead to the development of improved anticonvulsant treatments and to methods to prevent onset of seizures in some individuals.